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Oral delivery of exenatide-loaded hybrid zein nanoparticles for stable blood glucose control and β-cell repair of type 2 diabetes mice
BACKGROUND: Exenatide is an insulinotropic peptide drug for type 2 diabetes treatment with low risk of hypoglycemia, and is administrated by subcutaneous injection. Oral administration is the most preferred route for lifelong treatment of diabetes, but oral delivery of peptide drug remains a signifi...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189518/ https://www.ncbi.nlm.nih.gov/pubmed/32345323 http://dx.doi.org/10.1186/s12951-020-00619-0 |
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author | Bao, Xiaoyan Qian, Kang Yao, Ping |
author_facet | Bao, Xiaoyan Qian, Kang Yao, Ping |
author_sort | Bao, Xiaoyan |
collection | PubMed |
description | BACKGROUND: Exenatide is an insulinotropic peptide drug for type 2 diabetes treatment with low risk of hypoglycemia, and is administrated by subcutaneous injection. Oral administration is the most preferred route for lifelong treatment of diabetes, but oral delivery of peptide drug remains a significant challenge due to the absorption obstacles in gastrointestinal tract. We aimed to produce exenatide-loaded nanoparticles containing absorption enhancer, protectant and stabilizer using FDA approved inactive ingredients and easy to scale-up method, and to evaluate their long-term oral therapeutic effect in type 2 diabetes db/db mice. RESULTS: Two types of nanoparticles, named COM NPs and DIS NPs, were fabricated using anti-solvent precipitation method. In COM NPs, the exenatide was complexed with cholic acid and phosphatidylcholine to increase the exenatide loading efficiency. In both nanoparticles, zein acted as the cement and the other ingredients were embedded in zein nanoparticles by hydrophobic interaction. Casein acted as the stabilizer. The nanoparticles had excellent lyophilization, storage and re-dispersion stability. Hypromellose phthalate protected the loaded exenatide from degradation in simulated gastric fluid. Cholic acid promoted the intestinal absorption of the loaded exenatide via bile acid transporters. The exenatide loading efficiencies of COM NPs and DIS NPs were 79.7% and 53.6%, respectively. The exenatide oral pharmacological availability of COM NPs was 18.6% and DIS NPs was 13.1%. COM NPs controlled the blood glucose level of the db/db mice well and the HbA(1c) concentration significantly decreased to 6.8% during and after 7 weeks of once daily oral administration consecutively. Both DIS NPs and COM NPs oral groups substantially increased the insulin secretion by more than 60% and promoted the β-cell proliferation by more than 120% after the 7-week administration. CONCLUSIONS: Both COM NPs and DIS NPs are promising systems for oral delivery of exenatide, and COM NPs are better in blood glucose level control than DIS NPs. Using prolamin to produce multifunctional nanoparticles for oral delivery of peptide drug by hydrophobic interaction is a simple and effective strategy. |
format | Online Article Text |
id | pubmed-7189518 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-71895182020-05-04 Oral delivery of exenatide-loaded hybrid zein nanoparticles for stable blood glucose control and β-cell repair of type 2 diabetes mice Bao, Xiaoyan Qian, Kang Yao, Ping J Nanobiotechnology Research BACKGROUND: Exenatide is an insulinotropic peptide drug for type 2 diabetes treatment with low risk of hypoglycemia, and is administrated by subcutaneous injection. Oral administration is the most preferred route for lifelong treatment of diabetes, but oral delivery of peptide drug remains a significant challenge due to the absorption obstacles in gastrointestinal tract. We aimed to produce exenatide-loaded nanoparticles containing absorption enhancer, protectant and stabilizer using FDA approved inactive ingredients and easy to scale-up method, and to evaluate their long-term oral therapeutic effect in type 2 diabetes db/db mice. RESULTS: Two types of nanoparticles, named COM NPs and DIS NPs, were fabricated using anti-solvent precipitation method. In COM NPs, the exenatide was complexed with cholic acid and phosphatidylcholine to increase the exenatide loading efficiency. In both nanoparticles, zein acted as the cement and the other ingredients were embedded in zein nanoparticles by hydrophobic interaction. Casein acted as the stabilizer. The nanoparticles had excellent lyophilization, storage and re-dispersion stability. Hypromellose phthalate protected the loaded exenatide from degradation in simulated gastric fluid. Cholic acid promoted the intestinal absorption of the loaded exenatide via bile acid transporters. The exenatide loading efficiencies of COM NPs and DIS NPs were 79.7% and 53.6%, respectively. The exenatide oral pharmacological availability of COM NPs was 18.6% and DIS NPs was 13.1%. COM NPs controlled the blood glucose level of the db/db mice well and the HbA(1c) concentration significantly decreased to 6.8% during and after 7 weeks of once daily oral administration consecutively. Both DIS NPs and COM NPs oral groups substantially increased the insulin secretion by more than 60% and promoted the β-cell proliferation by more than 120% after the 7-week administration. CONCLUSIONS: Both COM NPs and DIS NPs are promising systems for oral delivery of exenatide, and COM NPs are better in blood glucose level control than DIS NPs. Using prolamin to produce multifunctional nanoparticles for oral delivery of peptide drug by hydrophobic interaction is a simple and effective strategy. BioMed Central 2020-04-28 /pmc/articles/PMC7189518/ /pubmed/32345323 http://dx.doi.org/10.1186/s12951-020-00619-0 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Bao, Xiaoyan Qian, Kang Yao, Ping Oral delivery of exenatide-loaded hybrid zein nanoparticles for stable blood glucose control and β-cell repair of type 2 diabetes mice |
title | Oral delivery of exenatide-loaded hybrid zein nanoparticles for stable blood glucose control and β-cell repair of type 2 diabetes mice |
title_full | Oral delivery of exenatide-loaded hybrid zein nanoparticles for stable blood glucose control and β-cell repair of type 2 diabetes mice |
title_fullStr | Oral delivery of exenatide-loaded hybrid zein nanoparticles for stable blood glucose control and β-cell repair of type 2 diabetes mice |
title_full_unstemmed | Oral delivery of exenatide-loaded hybrid zein nanoparticles for stable blood glucose control and β-cell repair of type 2 diabetes mice |
title_short | Oral delivery of exenatide-loaded hybrid zein nanoparticles for stable blood glucose control and β-cell repair of type 2 diabetes mice |
title_sort | oral delivery of exenatide-loaded hybrid zein nanoparticles for stable blood glucose control and β-cell repair of type 2 diabetes mice |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189518/ https://www.ncbi.nlm.nih.gov/pubmed/32345323 http://dx.doi.org/10.1186/s12951-020-00619-0 |
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